Investigations in this laboratory continue to examine the regulatory role of lymphocytes and macrophages in connective tissue metabolism. The influx of mononuclear cells into the synovium in rheumatoid arthritis appears to influence the hyperplasia of synovial fibroblasts which produce excessive levels of the inflammatory mediators, collagenase and prostaglandins. Lymphocytes and macrophages can stimulate this fibroblast growth and regulate fibroblast function via soluble intercellular signals, lymphokines and monokines. The mediators are being characterized, purified and messenger RNA isolated for trnaslation of these mononuclear cell products. Subpopulations of fibroblast target cells which specifically respond to these mediators are being cloned and identified by specific cell surface receptors and by unique functional capabilities. The T cell dependence of the synovial fibroplasia is emphasized by the histopathology of the tissues. Synovial tissues from one subset of arthritis patients (anergic) have intense T cell infiltration, a high ratio of helper:suppressor T cells and many HLA-DR+ cells. These synovia also have more synovial lining cell hyperplasia. In contrast, another subset (nonanergic) of patients have few T cells and also have less fibroplasia. The T cells isolated from inflamed synovium constitutively produce factors which stimulate fibroblast growth. Additional studies indicate that peripheral blood mononuclear cell immune function reflects immunopathologic events in the effected joint. These data provide insight into potential pathogenic mechanisms associated with rheumatoid arthritis.